Fluticasone Furoate/umeclidinium/vilanterol Research Articles

The long-term clinical and economic benefits of treating advanced COPD patients with single-inhaler triple therapy in Quebec, Canada – The IMPACT trial

BackgroundThis cost-utility analysis assessed the long-term clinical and economic benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy vs FF/VI or UMEC/VI from a Quebec societal perspective in patients with chronic obstructive pulmonary disease (COPD) with ≥1 moderate/severe exacerbation in the previous year. MethodsThe validated GALAXY disease progression model was utilized, with parameters set to baseline and efficacy data from IMPACT. Treatment costs (2017 Canadian dollars [C$]) were estimated using Quebec-specific unit costs. Costs and health outcomes were discounted at 1.5 %/year. A willingness-to-pay threshold of C$50,000/quality-adjusted life year (QALY) was considered cost-effective. Outcomes modeled were exacerbation rates, QALYs, life years (LYs), costs and incremental cost-effectiveness ratios (ICERs). Subgroup analyses were performed according to prior treatment, exacerbation history in the previous year, and baseline lung function. ResultsOver a lifetime horizon, FF/UMEC/VI resulted in more QALYs and LYs gained, at a small incremental cost compared with FF/VI and UMEC/VI. From a societal perspective, the estimated ICER for the base case was C$18,152/QALY vs FF/VI, and C$15,847/QALY vs UMEC/VI. For the subgroup analyses (FF/UMEC/VI compared with FF/VI and UMEC/VI), ICERs ranged from: C$17,412–25,664/QALY and C$16,493–18,663/QALY (prior treatment); C$15,247–19,924/QALY and C$15,444–28,859/QALY (exacerbation history); C$14,025–34,154/QALY and C$16,083–17,509/QALY (baseline lung function). InterpretationFF/UMEC/VI was predicted to improve outcomes and be cost-effective vs both comparators in the base case and all subgroup analyses, and based on this analysis would be an appropriate investment of health service funds in Quebec. Clinical trial registration numberIMPACT trial NCT02164513.

Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study

BackgroundCompared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score....

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study

BackgroundLimited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. ObjectiveTo explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β2-agonist (SABA) usage to determine the clinical relevance of moderate events. MethodsCAPTAIN was a Phase IIIA 24–52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β2-agonist. Outcomes reportedinclude: first post-randomization exacerbation event by severity (Weeks 1–52), frequency and duration of moderate and severe exacerbations and time course of changes over ±14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. ResultsOf the intent-to-treat population (N=2436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after ∼8–12 days for both exacerbation severities. ConclusionWhile severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes. NCT02924688.

Outcomes of Patients with COPD Treated with ICS/LABA Before and After Initiation of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI).

Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA). This retrospective cohort study included commercial and Medicare Advantage with PartD administrative claims data from September01, 2016, to March31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017-March 2019). The 12months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. The overall population included 1449 patients (mean age 70.75years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI.

Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study

BackgroundFindings from CAPTAIN (NCT02924688) suggest treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 (T2) inflammation markers in patients with moderate-to-severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. ObjectiveTo investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting β2-agonist combination FF/VI, or doubling FF dose. MethodsPrespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough forced expiratory volume in 1 second, FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire, ACQ]) following addition of UMEC to FF/VI or doubling FF dose in FF/VI or FF/UMEC/VI. ResultsAdding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling FF dose across all baseline characteristics assessed. Doubling FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling FF dose generally led to improvements in ACQ scores irrespective of baseline characteristics. ConclusionUnlike previous findings with T2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.

Characterization of Patients with Asthma Initiating Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)

Characterization of Patients with Asthma Initiating Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)

Outcomes Following Initiation of Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol versus Multiple-Inhaler Triple Therapy Among Medicare Advantage with Part D Beneficiaries and Those Commercially Enrolled for Health Care Insurance in the United States.

Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US. Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators. In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant. FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.

Real-World Study of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol on Asthma Control in the US.

Real-world asthma control data among patients initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are limited. This study assessed rescue medication use and asthma-related exacerbations in patients with asthma before and after initiating single-inhaler FF/UMEC/VI using administrative claims data. This retrospective, pre-post cohort study analyzed data from the IQVIA PharMetrics Plus database (September 18, 2016‒March 31, 2020). Patients aged ≥18 years that had ≥1 dispensing of single-inhaler FF/UMEC/VI 100/62.5/25 mcg (first dispensing = index date), ≥12 months of continuous health insurance enrollment prior to (pre-treatment) and following (post-treatment) FF/UMEC/VI initiation and ≥1 diagnosis of asthma during the pre-treatment period or on the index date were included. The primary endpoint was the number of oral corticosteroid (OCS) dispensings per patient per year during pre- and post-treatment periods. Secondary endpoints included asthma-related exacerbation rates and short-acting β2-agonist (SABA) use. Comparisons between pre- and post-treatment periods were made using risk and rate ratios. Overall, 890 patients with asthma initiating treatment with FF/UMEC/VI were included. The most recently dispensed controller medications prior to FF/UMEC/VI initiation were inhaled corticosteroids/long-acting β2-agonists (33.5%) and leukotriene modifiers (33.0%). Patients had a 29% reduction in the number of OCS dispensings (rate ratio [95% confidence interval (CI)]: 0.71 [0.65, 0.77], P < 0.001) during post-treatment versus pre-treatment, with a 23% reduction in the proportion of patients with ≥1 OCS dispensing post-treatment (risk ratio [95% CI]: 0.77 [0.73, 0.82], P < 0.001). Significant reductions in rates (rate ratio [95% CI]) of asthma-related exacerbations (0.59 [0.52, 0.67], P < 0.001) and SABA use (0.80 [0.74, 0.86], P < 0.001) were also observed. In this real-world study, patients with asthma had significantly lower OCS use, asthma-related exacerbations, and SABA use following treatment initiation with FF/UMEC/VI compared with their pre-treatment period. These results suggest better asthma control following initiation of FF/UMEC/VI in a routine clinical practice setting.

Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging

BackgroundSmall airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting β2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised.MethodsThree-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests.ResultsAcross inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0–54.1%) versus FF/UM/VI (20.8–22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9–23.6%) versus FF/UM/VI (6.8–8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p < 0.001), overall and for treatment components; notably, regional small airways deposition of the ICS components was approximately five-fold greater with budesonide versus fluticasone furoate (16.1% vs. 3.3%).ConclusionsBGF was associated with greater total, central, and small airways deposition for all components versus FF/UM/VI. Importantly, using an identical inhalation profile, there was an approximately five-fold difference in small airways deposition for the ICS components, with only a small percentage of the ICS from FF/UM/VI reaching the small airways. Further research is needed to understand if the enhanced delivery of BGF translates to clinical benefits.Graphical

Mortality risk reduction with budesonide/glycopyrrolate/formoterol fumarate versus fluticasone furoate/umeclidinium/vilanterol in COPD: a matching-adjusted indirect comparison based on ETHOS and IMPACT

ABSTRACT Objective Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. While two approved fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) triple therapies reduce all-cause mortality (ACM) versus dual LAMA/LABA therapy in patients with COPD, head-to-head studies have not compared the effects of these therapies on ACM. We compared ACM in adults with moderate-to-very severe COPD receiving budesonide/glycopyrrolate/formoterol fumarate (BGF) in ETHOS versus fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in IMPACT using a matching-adjusted indirect comparison (MAIC). Methods A systematic literature review identified two studies (ETHOS [NCT02465567]; IMPACT [NCT02164513]) of ≥52 weeks reporting ACM as an efficacy endpoint in patients receiving triple therapy. As ETHOS and IMPACT lack a common comparator, an unanchored MAIC compared ACM between licensed doses of BGF (320/18/9.6 μg) from ETHOS and FF/UMEC/VI (100/62.5/25 μg) from IMPACT in patients with moderate-to-very severe COPD. Using on- and off-treatment data from the final retrieved datasets of the intention-to-treat populations, BGF data were adjusted according to aggregate FF/UMEC/VI data using 11 baseline covariates; a supplementary unadjusted indirect treatment comparison was also conducted. P-values for these post-hoc analyses are not adjusted for Type I error. Results ACM over 52 weeks was statistically significantly reduced by 39% for BGF versus FF/UMEC/VI in the MAIC (hazard ratio [HR] [95% CI]: 0.61 [0.38, 0.95], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019). Conclusion In this MAIC, which adjusted for population heterogeneity between ETHOS and IMPACT, ACM was significantly reduced with BGF versus FF/UMEC/VI in patients with moderate-to-very severe COPD.

Budget Impact Analysis of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Asthma in the Dubai Academic Healthcare Corporation.

Asthma is a common, chronic respiratory disorder associated with substantial societal and economic burden globally, despite the availability of different treatment modalities. GSK has developed a once-daily single-inhaler triple therapy (SITT), comprised of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI); a combination of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist for patients with uncontrolled asthma. A budget impact analysis was conducted to determine the financial impact of introducing FF/UMEC/VI SITT from the perspective of the Dubai Academic Healthcare Corporation (DAHC). A budget impact model was constructed using an epidemiology-based approach and used to estimate the expected 5-year budget impact of including FF/UMEC/VI for the treatment of eligible patients within the DAHC in the United Arab Emirates (UAE). The model included both pharmacy and efficacy-related costs. The perspective of the DAHC healthcare payer was adopted, thus only direct payer costs were included in the analysis. A one-way sensitivity analysis was conducted to test the robustness of the model structure, assumptions, and input parameters. The total budget impact was estimated to save 1 million United States Dollars (USD) over 5 years, with budget impacts of 0.08 million USD in Year 1; 0.14 million USD in Year 2; 0.22 million USD in Year 3; 0.28 million USD in Year 4; and 0.33 million USD in Year 5. The overall budget impact per patient was estimated to save 12.2 USD over 5 years. In one-way sensitivity analyses, the budget impact was most sensitive to changes in the market uptake of FF/UMEC/VI. Healthcare payers may consider FF/UMEC/VI in the management of uncontrolled asthma which would save costs and reduce healthcare resource use in the UAE.

Healthcare Resource Utilization, Cost and Clinical Outcomes in Patients Diagnosed with COPD Initiating Tiotropium Bromide/Olodaterol versus Fluticasone Furoate/Umeclidinium/Vilanterol Based on Exacerbation History.

ATS and GOLD guidelines recommend treating low-exacerbation risk COPD patients with dual (LAMA/LABA) agents and reserving triple therapy (TT; LAMA/LABA and inhaled corticosteroids [ICS]) for severe cases with higher-exacerbation risk. However, TT often is prescribed across the COPD spectrum. This study compared COPD exacerbations, pneumonia diagnosis, healthcare resource utilization, and costs for patients initiating tiotropium bromide/olodaterol (TIO/OLO) and a TT, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), stratified by exacerbation history. COPD patients who initiated TIO/OLO or FF/UMEC/VI between 06/01/2015-11/30/2019 (index date=first pharmacy fill-date with ≥30 consecutive treatment days) were identified from the Optum Research Database. Patients were ≥40 years old and continuously enrolled for 12 months during the baseline period and ≥30 days during follow-up. Patients were stratified into GOLD A/B (0-1 baseline non-hospitalized exacerbation), No exacerbation (subset of GOLD A/B), and GOLD C/D (≥2 non-hospitalized and/or ≥1 hospitalized baseline exacerbation). Baseline characteristics were balanced with propensity score matching (1:1). Adjusted risks of exacerbation, pneumonia diagnosis, and COPD and/or pneumonia-related utilization and costs were evaluated. Adjusted exacerbation risk was similar in GOLD A/B and No exacerbation subgroups, and lower in GOLD C/D for FF/UMEC/VI versus TIO/OLO initiators (hazard ratio: 0.87; 95% CI: 0.78, 0.98, p=0.020). Adjusted pneumonia risk was similar between cohorts across the GOLD subgroups. Adjusted COPD and/or pneumonia-related population annualized pharmacy costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators across subgroups, p<0.001.Adjusted COPD and/or pneumonia-related population annualized total healthcare costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators in the GOLD A/B and No exacerbation, subgroups, p<0.001 (cost ratio [95% CI]: 1.25 [1.13, 1.38] and 1.21 [1.09, 1.36], respectively), but similar in the GOLD C/D subgroup. These real-world results support ATS and GOLD recommendations for treating low-exacerbation risk COPD patients with dual bronchodilators and TT for more severe, higher-exacerbation risk COPD patients.

COPD Exacerbations, Costs, and Health Care Resource Utilization Before and After Initiation of Fluticasone Furoate/Umeclidinium/Vilanterol in Routine Care in the USA.

To examine the impact of initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in a single device on chronic obstructive pulmonary disease (COPD) exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related healthcare resource utilization (HCRU) and costs in patients with COPD. Retrospective database analysis of patients with COPD aged ≥40 years who initiated FF/UMEC/VI between September 1, 2017, and December 31, 2018 (index date: first pharmacy claim for FF/UMEC/VI), following evidence of multiple-inhaler triple therapy (MITT) (≥30 consecutive days) in the year prior to index. COPD exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related HCRU and costs were compared between the baseline period (12 months prior to and including index) and follow-up period (12 months following index). Data from 912 patients (mean [SD] age: 71.2 [8.1], 51.2% female) were included in the analyses. Among the overall cohort, mean count of total COPD exacerbations (moderate or severe) per patient was statistically significantly lower in the follow-up period compared to baseline (1.2 vs 1.4, p=0.001). The proportion of patients with ≥1 COPD exacerbation (moderate or severe) was also statistically significantly lower in the follow-up period compared to baseline (56.4% vs 62.4%, p=0.001). All-cause and COPD-related HCRU were similar during follow-up compared to baseline, although the proportion of patients with COPD-related ambulatory visits was lower during follow-up (p<0.001). COPD-related office visit costs, emergency room visit costs, and pharmacy costs were statistically significantly lower during follow-up compared to baseline (p<0.001; p=0.019; p<0.001, respectively). In a real-world setting, patients on MITT who subsequently initiated FF/UMEC/VI in a single device had significant reductions in the rate of COPD exacerbations (moderate or severe). Switching to FF/UMEC/VI also resulted in improvements in some HCRU and cost outcomes. These data support the use of FF/UMEC/VI among patients at high risk of exacerbation to reduce future risk and improve outcomes.

In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler.

Background: Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. Materials and Methods: The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. Results: During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. Conclusions: Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.

Cost-Effectiveness of Once-Daily Single-Inhaler COPD Triple Therapy in Spain: IMPACT Trial.

Given between-country differences in healthcare systems, treatment costs, and disease management guidelines, country-specific cost-effectiveness analyses are important. This study evaluated the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI among patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations from a Spanish healthcare system perspective. Baseline data and treatment effects from the IMPACT trial were populated into the validated GALAXY COPD progression model. Utilities were estimated using Spanish observational data. Direct healthcare costs (2019 €) were informed by Spanish public sources. A 3% discount rate for costs and benefits was applied. The time horizon and treatment duration were 3 years (base case). One-way sensitivity, scenario, and probabilistic sensitivity analyses were performed. FF/UMEC/VI treatment resulted in fewer exacerbations over 3 years (4.130 vs 3.648) versus FF/VI, with a mean (95% confidence interval [CI]) incremental cost of €444 (€149, €713) per patient and benefit of 0.064 (0.053, 0.076) quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €6887 per QALY gained. FF/UMEC/VI was a dominant treatment strategy versus UMEC/VI, resulting in fewer exacerbations (4.130 vs 3.360), with a mean (95% CI) incremental cost of -€450 (-€844, -€149) and benefit of 0.054 (0.043, 0.064) QALYs. FF/UMEC/VI was cost-effective versus FF/VI and UMEC/VI across all analyses. FF/UMEC/VI was predicted to be a cost-effective treatment option versus FF/VI or UMEC/VI in symptomatic COPD patients at risk of exacerbations in Spain, across all scenarios and sensitivity analyses.

SA7 Reduced Health Care Resource Utilisation and Costs Following a Switch From Multiple-Inhaler to Once-Daily Single-Inhaler Triple Therapy in COPD Patients in a Real-World Primary Care Setting in England

To investigate all-cause and chronic obstructive pulmonary disease (COPD)-related health care resource utilisation (HCRU) and direct medical costs in patients with COPD before and after switching from multiple-inhaler triple therapy (MITT) to once-daily single-inhaler triple therapy (SITT) fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI).

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis

BackgroundSmoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. MethodsIMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. ResultsOf the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. ConclusionsFF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registrationGSK (CTT116855/NCT02164513).

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region

BackgroundThe most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region.MethodsA budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset).ResultsOur analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination.ConclusionA pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

Effect of Recent Exacerbation History on the Efficacy of Once-Daily Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease in the FULFIL Trial.

BackgroundIn the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.MethodsFULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George’s respiratory questionnaire total score at Week 24.ResultsOf the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.ConclusionFF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.

Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis.

IntroductionRandomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.MethodsThis NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George’s Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).ResultsThe NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).ConclusionThe findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02231-0.